Uridine-5′-diphosphosulfoquinovose (UDP-SQ) is a unique sugar nucleotide which carries a negative charge at its sulfonate group. UDP-SQ is believed to react with sugar nucleotide-dependent glycosyltransferases and donate its sulfonate group to other substrates in order to form valuable compounds including, but not limited to, 6-sulfo-α-D-quinovosyl diacyglycerol (SQDG). UDP-SQ is thought to be the direct precursor of SQDG, to which it donates its unique sulfonic acid head group, sulfoquinovose. However, there is not a simple, rapid method of synthesizing UDP-SQ, or an efficient method for subsequent modification of UDP-SQ to compounds including, but not limited to, SQDG and alkyl sulfoquinovoside.
SQDG is an abundant sulfur-containing non-phosphorous glycerolipid that is specifically associated with photosynthetic (thylakoid) membranes of higher plants, mosses, ferns, algae, and most photosynthetic bacteria. SQDG is universally associated with oxygenic photosynthesis and is an important component of the biological sulfur cycle.
SQDG has also been shown to be a potent inhibitor of several mammalian DNA polymerases and Human Immunodeficiency Virus Reverse Transcriptase 1 (HIV-RT1), and as such, is valuable as an anti-viral compound. (Ohta et al., “Sulfoquinovosyldiacylglycerol, KM043, a new potent inhibitor of eukaryotic DNA polymerases and HIV-reverse transcriptase type 1 from a marine red alga, Gigartina tenella,” Chem. Pharm. Bull., 46(4): 684-86 (1998)). Moreover, SQDG has also been demonstrated to be valuable due to its anti-tumor promoting properties and its ability to enhance the cytocidal effects of anti-cancer chemotherapy agents. (Shirahashi et al., “Isolation and Identification of Anti-tumor-Promoting Principles from the Fresh-Water Cyanobacterium Phormidium tenue,” Chem. Pharm. Bull., 41(9): 1664-66 (1993)). Furthermore, SQDG is commonly thought to have excellent detergent properties. (Benson, A. A., “The Plant Sulfolipid,” Adv. Lipid Res., 1: 387-94 (1963)). Thus, a method of producing UDP-SQ, and its subsequent modification to compounds including, but not limited to, SQDG, is desirable.
Traditionally, UDP-SQ has been synthesized through a series of chemical reactions. (Heinz et al., “Synthesis of different nucleoside 5′-diphospho-sulfoquinovoses and their use for studies on sulfolipid biosynthesis in chloroplasts,” Eur. J. Biochem., 184: 445-453 (1989)). However, this chemical production is highly involved, results in low yields of UDP-SQ, and requires several days to complete. (Id.) Moreover, previous studies of SQDG required time-consuming isolation and purification of the anionic sulfolipid from photosynthetic organisms. (Ohta et al., “Action of a New Manumalian DNA Polymerase Inhibitor, Sulfoquinovosyl diacylglycerol,” Biol. Pharm. Bull., 22(2): 111-16 (1999); Gustafson et al., “AIDS-Antiviral Sulfolipids From Cyanobacteria (Blue-Green Algae),” J. Natl. Cancer Inst., 81: 1254-258 (1989)). Thus, what is needed is a more simple, rapid method of synthesizing UDP-SQ, and for the subsequent modification of UDP-SQ to compounds including, but not limited to, SQDG.